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Published on: March 20, 2018
Effects of Repeated Early-life Anesthesia Exposure on Visual System Development in Mice
Célia Seillier1, Amandine Élodie Bonnet2, Shahad Albadri3
1Institut Blood and Brain at Caen-Normandy, UMR-S U1237/Physiopathology and Imaging of Neurological Disorders, Normandy University, UNICAEN, INSERM, GIP Cyceron, Caen, France. Current address: GliaLab and the Letten Centre, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Insights
Repeated early general anesthesia in mice impairs visual development and function. Altered tissue-type plasminogen activator (tPA) pathways may mediate these neurodevelopmental effects, suggesting tPA as a vulnerability marker.
Area of Science:
- Neuroscience
- Developmental Biology
- Anesthesiology
Background:
- Millions of children undergo general anesthesia annually, raising concerns about long-term neurodevelopmental effects.
- Previous research indicated single early anesthesia exposure can impair visual attention in children.
- This study examines the impact of repeated early general anesthesia on visual system maturation in mice.
Purpose of the Study:
- To investigate the effects of repeated early general anesthesia on visual system development in mice.
- To explore the role of tissue-type plasminogen activator (tPA) in mediating anesthesia-induced neurodevelopmental alterations.
- To identify potential biomarkers for anesthesia-related neurodevelopmental vulnerability.
Main Methods:
- Male SWISS and C57BL/6J mice (wild-type or tPA-deficient) were exposed to isoflurane anesthesia daily from postnatal day 4-10.
- Control mice received oxygen alone.
- Visual system integrity, inflammation, and tPA levels were assessed using behavioral tests, imaging, and immunohistochemistry.
Main Results:
- Anesthesia exposure delayed eyelid opening and caused lasting deficits in depth perception and oculomotor reflexes.
- Retinal and primary visual cortex thickness were significantly reduced in exposed mice.
- Lower circulating tPA levels were observed in anesthesia-exposed mice, and tPA-deficient mice showed attenuated visual alterations.
Conclusions:
- Early repeated general anesthesia disrupts visual system maturation in mice.
- Altered tPA pathways are implicated in these neurodevelopmental effects.
- tPA may serve as a potential marker for anesthesia-related neurodevelopmental vulnerability.
Background:
General anesthesia is administered to millions of children annually, yet its long-term effects on neurodevelopment remain a concern. It was previously reported that even a single early exposure to general anesthesia for minor surgery impairs visual attention in children. This study investigates the effects of early repeated general anesthesia exposure on visual system maturation in mice and explores the role of tissue-type plasminogen activator in mediating these effects during development.
Methods:
Male SWISS and C57BL/6J mice (wild-type or deficient for tissue-type plasminogen activator) were exposed to general anesthesia with 1.3% isoflurane in 50% oxygen for 90 min per day from postnatal days 4 to 10. Control animals received 50% oxygen alone. Visual system integrity and inflammation were assessed at postnatal day 15 and at 6 weeks using behavioral tests, high-resolution imaging, and immunohistochemistry. In SWISS mice, circulating tissue-type plasminogen activator levels were measured using a biochemical approach, and neurovascular coupling was evaluated by functional ultrasound imaging.
Results:
Early repeated general anesthesia exposure delayed eyelid opening (median postnatal day 13 [95% CI, 0.52 to 1.45] vs. postnatal day 15 [95% CI, 0.62 to 1.92]; P < 0.0001), caused lasting visual function deficits (depth perception and oculomotor reflex), and reduced retinal (0.2627 ± 0.04 mm vs. 0.1667 ± 0.03 mm; P < 0.0001) and primary visual cortex thickness (0.8000 ± 0.08 mm vs. 0.7282 ± 0.05 mm; P = 0.0235). Notably, lower circulating tissue-type plasminogen activator levels were observed in general anesthesia-exposed SWISS mice (11.580 ± 2.19 ng/ml vs. 7.654 ± 1.31 ng/ml; P = 0.0082). Tissue-type plasminogen activator-deficient mice exhibited attenuated or absent general anesthesia-induced visual alterations.
Conclusions:
These findings indicate that early repeated exposure to general anesthesia disrupts visual system maturation in mice and suggest that altered tissue-type plasminogen activator pathways may contribute to these effects, identifying tissue-type plasminogen activator as a potential marker of anesthesia-related neurodevelopmental vulnerability. Additional experimental work will be required to further support this association and clarify its underlying mechanisms.
